NMR-based conformational analysis of 2',6-disubstituted uridines and antiviral evaluation of new phosphoramidate prodrugs

Bioorg Med Chem. 2015 Sep 1;23(17):5809-15. doi: 10.1016/j.bmc.2015.07.003. Epub 2015 Jul 10.

Abstract

Six novel phosphoramidate prodrugs of uridine analogues, with structural modifications introduced at the 6- and 2',6-positions, have been prepared and evaluated for selective antiviral activity against hepatitis C virus, as well as other positive-stranded RNA viruses. An analysis of the conformational properties of the parent nucleosides was carried out using two-dimensional NMR spectroscopy based experiments, highlighting a 3'-endo (North) sugar puckering preference and syn orientation.

Keywords: Conformation; HCV; Nucleosides; Phosphoramidates; Prodrugs.

MeSH terms

  • Humans
  • Magnetic Resonance Spectroscopy / methods*
  • Molecular Conformation
  • Molecular Structure
  • Nucleosides / chemistry*
  • Prodrugs / chemistry*
  • Uridine / analogs & derivatives
  • Uridine / chemistry*

Substances

  • Nucleosides
  • Prodrugs
  • Uridine